Citations

Abstract Humanity is facing an important existential threat—irreversible climate change caused by human activity. Until recently, most of the proposals to address climate change have downplayed or ignored the adverse impact of food systems, especially intensive animal agriculture. This is in spite of the fact that up to a third of global greenhouse gas production to date can be attributed to animal agriculture. Recent developments at COP28 have signaled that the tide is turning, however, and that food systems are becoming part of global discussions on climate change solutions. The pressing nature of irreversible climate change requires rethinking our food systems. To solve the climate change crisis, we propose transitioning to a predominantly plant-based diet, and phasing out intensive animal agriculture as diets shift, without increasing pastoral farming. We suggest that such transformations in global food systems can be accomplished largely through education and large-scale public information campaigns, removal of subsidies, taxation to account for externalized costs of animal agriculture, improved labelling of products, and various investment/divestment drivers. Better metrics and industry benchmarks involving food and agriculture-specific performance indicators that reflect food system sustainability will be important. Increased global awareness of these issues and a change in mindset (which will drive political will) also are needed. Our current trajectory is untenable, and we must begin to turn the ship now towards sustainable food systems and diets.

Abstract Pharmacogenomics (PGx) is focused on the relationship between an individual's genetic makeup and their response to medications, with the overarching aim of guiding prescribing decisions to improve drug efficacy and reduce adverse events. The PGx and genomic medicine communities have worked independently for over 2 decades, developing separate standards and terminology, making implementation of PGx across all areas of genomic medicine difficult. To address this issue, the Clinical Genome Resource (ClinGen) Pharmacogenomics Working Group (PGxWG) was established by the National Institutes of Health (NIH)-funded ClinGen to initially create frameworks for evaluating gene–drug response clinical validity and actionability aligned with the ClinGen frameworks for evaluating monogenic gene–disease relationships, and a framework for classifying germline PGx variants similar to the American College of Medical Genetics (ACMG) and Association of Molecular Pathology (AMP) system for interpretation of disease-causing variants. These frameworks will leverage decades of work from well-established PGx resources facilitating buy-in among PGx stakeholders. In this report, we describe the background and major activities of the ClinGen PGxWG, and how this initiative will facilitate the critical inclusion of PGx into the larger context of genomic medicine.

Abstract Pancreatic cancer is a devastating malignancy in great need of new and more effective treatment approaches. In recent years, studies have indicated that nutritional interventions, particularly nutraceuticals, may provide novel avenues to modulate cancer progression. Here, our study characterizes the impact of ω-3 polyunsaturated fatty acids, eicosapentaenoic acid, and docosahexaenoic acid, as a nutraceutical intervention in pancreatic cancer using a genetically engineered mouse model driven by KrasG12D and Trp53R172H. This model closely resembles human pancreatic carcinogenesis, offering a disease relevant platform for translational research. Our findings showed that ω-3 polyunsaturated fatty acids intervention (using a diet supplemented with 6% cod liver oil) significantly reduced tumor volume as well as lung and liver metastasis and a trend toward improved survival rate compared with control treated mice. This antitumoral effect was accompanied by distinct changes in tumor membrane fatty acid profile and eicosanoids release. Furthermore, the eicosapentaenoic acid and docosahexaenoic acid intervention also reduced malignant histological parameters and induced apoptosis without affecting cell proliferation. Of note is the significant reduction in tumor fibrosis that was associated with decreased levels of Sonic Hedgehog, a major ligand controlling this cellular compartment in pancreatic cancer. All together our results demonstrate the impact of eicosapentaenoic acid and docosahexaenoic acid as antitumor regulators in pancreatic cancer, suggesting potential for ω-3 polyunsaturated fatty acids as a possible antitumoral dietary intervention. This research opens new avenues for integrating nutraceutical strategies in pancreatic cancer management.

Introduction: Trust and rapport between patients and physicians form the cornerstone of effective medical practice. A key factor influencing this trust is the patient’s perception of the physician’s appearance. Women physicians often face more rigorous expectations concerning their physical appearance compared to men physicians, creating a need to balance traditional professional attire with maintaining femininity and individuality. This review explores the unique challenges women physicians encounter in presenting a professional image. Methods: A narrative review was conducted using PubMed and Google Scholar to identify studies addressing both patient and physician perceptions of physician appearance. The search was limited to studies conducted in the United States and published between 2004 and 2024. Seven articles met the inclusion criteria and were selected for analysis. Results: The findings suggest that professional attire, particularly when combined with a white coat, is associated with higher perceptions of competence and professionalism. However, women physicians face ambiguity in meeting these expectations compared with men. In addition, women are more frequently mistaken for nurses, phlebotomists, or support staff based on their attire and appearance. Discussion: Overall, patients tend to prefer professional attire to physicians, but these preferences are influenced by cultural, demographic, and age-related factors. Women physicians, in particular, experience heightened scrutiny regarding their appearance and are subject to stricter norms than men physicians. This challenge is further amplified for young women trainees, who may struggle to convey professionalism due to their youthful appearance.

ABSTRACT Anorectal mucosal melanoma (ARMM) is exceptionally rare, highly malignant, and characterized by a poor prognosis. We present the case of a 76-year-old woman with ARMM and recurrent gastrointestinal (GI) bleeding/anemia caused by small-bowel metastases, which was successfully managed with laparoscopic resection. ARMM is an aggressive type of cancer that has the potential to metastasize to the GI tract approximately 4.5 years after the primary diagnosis. Intussusception and GI bleed are potential complications. Small-bowel metastatic melanoma typically goes undiagnosed until autopsy and requires a multidisciplinary approach. Key treatment options include surgery and immunotherapy to improve patient outcomes.

Juxtaglomerular cell tumor (JxGCT) is a rare type of renal neoplasm demonstrating morphologic overlap with some mesenchymal tumors such as glomus tumor (GT) and solitary fibrous tumor (SFT). Its oncogenic drivers remain elusive, and only a few cases have been analyzed with modern molecular techniques. In prior studies, loss of chromosomes 9 and 11 appeared to be recurrent. Recently, whole-genome analysis identified alterations involving genes of MAPK-RAS pathway in a subset, but no major pathogenic alterations have been discovered in prior whole transcriptome analyses. Considering the limited understanding of the molecular features of JxGCTs, we sought to assess a collaborative series with a multiomic approach to further define the molecular characteristics of this entity. Fifteen tumors morphologically compatible with JxGCTs were evaluated using immunohistochemistry for renin, single-nucleotide polymorphism array (SNP), low-pass whole-genome sequencing, and RNA sequencing (fusion assay). In addition, methylation analysis comparing JxGCT, GT, and SFT was performed. All cases tested with renin (n=11) showed positive staining. Multiple chromosomal abnormalities were identified in all cases analyzed (n=8), with gains of chromosomes 1p, 10, 17, and 19 and losses of chromosomes 9, 11, and 21 being recurrent. A pathogenic HRAS mutation was identified in one case as part of the SNP array analysis. Thirteen tumors were analyzed by RNA sequencing, with 2 revealing in-frame gene fusions: TFG::GPR128 (interpreted as stochastic) and NAB2::STAT6. The latter, originally diagnosed as JxGCT, was reclassified as SFT and excluded from the series. No fusions were detected in the remaining 11 cases; of note, no case harbored NOTCH fusions previously described in GT. Genomic methylation analysis showed that JxGCT, GT, and SFT form separate clusters, confirming that JxGCT represents a distinct entity (ie, different from GT). The results of our study show that JxGCTs are a distinct tumor type with a recurrent pattern of chromosomal imbalances that may play a role in oncogenesis, with MAPK-RAS pathway activation being likely a driver in a relatively small subset.

ResumenLa tabaquera anatómica, una región triangular en la porción dorso-radial de la muñeca, es un punto de referencia anatómico clave. Está delimitada por los tendones del extensor largo del pulgar, extensor corto del pulgar y abductor largo del pulgar, y alberga la arteria radial y ramas nerviosas. Patologías como quistes sinoviales, fracturas y osteofitos pueden alterar su apariencia. Estudios sobre lesiones del ligamento escafolunar (SLL) muestran que el daño crónico provoca el desplazamiento dorso-radial del escafoides, iniciando un proceso degenerativo conocido como colapso avanzado escafolunar (SLAC). Esto a menudo resulta en la "desaparición" de la tabaquera anatómica, lo que facilita la identificación de pacientes con muñeca SLAC junto con síntomas como dolor y rigidez. La afección es impulsada por la formación de osteofitos, subluxación del escafoides y sinovitis, lo que conduce a inestabilidad articular y deformidad. Los tratamientos tradicionales, como la estiloidectomía, pueden no resolver completamente la inestabilidad. Nuevos enfoques que consideran la dinámica tridimensional de la muñeca podrían ser más efectivos para manejar el SLAC. Estudios biomecánicos sugieren que las lesiones del SLL, junto con la pérdida de estabilizadores secundarios, provocan que el escafoides se pronuncie y flexione, resultando en una proyección dorso-radial dentro de la fosa del escafoides. Sin tratamiento, esto puede progresar a SLAC, frecuentemente caracterizado por el "bulto dorso-radial de la muñeca".

Abstract INTRODUCTION Psychotropic medication (PM) use in behavioral‐variant frontotemporal dementia (bvFTD) is higher than in other dementias. However, no information exists on whether PM use differs between sporadic and genetic bvFTD. METHODS We analyzed data from sporadic and genetic bvFTD participants with PM prescriptions in the Advancing Research and Treatment in Frontotemporal Lobar Degeneration/Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects study. We estimated ordinal odds ratio (OOR) of having more PM comparing sporadic and genetic bvFTD. Finally, we explored the neuropsychiatric symptom (NPS) combinations using classification and regression trees (CART). RESULTS We included 263 with sporadic and 193 with genetic bvFTD. The OOR for sporadic bvFTD to be on PM was 1.75 (95% confidence interval: 1.21 to 2.53) for the fully adjusted model. CART revealed the most common NPS combination was apathy + personality changes in 18% of participants. DISCUSSION Participants with sporadic bvFTD were twice as likely to be on PM compared to genetic bvFTD. The reason for increased PM usage in sporadic bvFTD participants should be further investigated. Highlights We report on patients with behavioral variant frontotemporal dementia (bvFTD). We evaluated the psychotropic medication (PM) prescription at baseline in the cohort. Patients with sporadic bvFTD had more prescriptions for PM than genetic patients. The frequency of symptoms combination was different in sporadic and genetic bvFTD.